Biomedical Engineering Reference
In-Depth Information
14.4 EmergingTrendswithDNAVaccinationwith
ElectroporationandItsPotentialImplications
14.4.1 Maximizing Both the Prophylactic and Therapeutic
Properties of DNA Vaccines
The.limitation.of.DNA.vaccines,.at.least.in.their.irst.generation.form,.is.obvious:.limited.
ability.to.generate.antibody.responses.in.large.animal.models.and.in.humans..This.limits.
the.use.of.DNA.vaccines.for.prophylactic.purposes,.as.many.preventative.vaccine.strate-
gies. require. a. strong. antibody. response.. However,. much. of. this. view. has. changed. due.
to.the.auspicious.immune.effects.of.DNA.vaccines.when.coupled.to.electroporation.
47
.In.
contrast. with. DNA. alone,. DNA. followed. by. electroporation. increases. both. cellular. and.
antibody. responses,. and. this. effect. can. be. observed. in. both. large. animals. (Figure 14.3a.
and.b).and.humans.(data.not.shown;.mentioned.above)..Although.more.clinical.evaluation.
is.required,.we.have.observed.that.the.mode.of.delivery.of.DNA.immunization.followed.
by. electroporation. dramatically. alters. the. vaccine-induced. response.. While. intramuscu-
lar. immunization. followed. by. electroporation. raises. strong. T. cell. responses. and. mod-
est.to.strong.antibody.responses,.intradermal.immunization.followed.by.electroporation.
dramatically.augments.vaccine-induced.antibody.responses.
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.As.shown.in.Figure 14.3b,.
electroporation. following. either. intramuscular. or. intradermal. immunization. greatly.
increased. antibody. responses. as. measured. by. antigen-speciic. endpoint. titer.. Moreover,.
the.effect.was.even.more.demonstrable.when.the.vaccines.were.delivered.intradermally.
with. electroporation.. This. trend. was. demonstrated. in. nonhuman. primates,. and. we. are.
currently.studying.this.phenomenon.in.humans.with.a.speciic.emphasis.on.developing.
strong.antibody-driving.vaccines.against.pathogens.such.as.inluenza.(H1N1.and.H5N1)..
Unlike. currently. approved. attenuated. vaccines,. electroporated. DNA. vaccines. could. be.
more.speciic.and.eficient.by.inducing.only.immune.responses.that.are.critical.for.the.host.
to. clear. the. pathogen,. and. unlike. subunit. vaccines,. electroporated. DNA. vaccines. could.
be. used. against. almost. all. pathogens. because. of. their. ability. to. raise. both. cellular. and.
humoral.immune.responses..Much.like.the.next.generation.of.novel.cancer.drugs,.which.
inhibit. cancer-speciic. pathways,. DNA. vaccination. with. electroporation. could. also. pro-
vide.speciicity.by.inducing.only.the.immune.response.required.for.clearing.the.virus.and.
not.inducing.unnecessary.responses.
14.4.2 Developing Multicomponent and Universal Vaccines
Although.the.concept.of.DNA.vaccines.has.been.around.since.the.early.1990s,.their.full.
potential.is.only.now.being.realized..First,.the.magnitude.of.cellular.and.humoral.immune.
responses.with.DNA.vaccines.plus.electroporation.in.humans.and.larger.animals.is.sig-
niicantly.greater.than.that.observed.in.other.previous.DNA-alone.studies..Thus,.clinical.
trials.with.DNA.and.electroporation.will.provide.the.irst.realistic.opportunity.to.evaluate.
the.eficacy.of.DNA.vaccines.in.humans..Second,.use.of.cytokine-.and.chemokine-encod-
ing.plasmids.will.be.the.foundation.for.the.next.generation.of.electroporation-delivered.
vaccines.by.targeting.pathogens.more.speciically.and.potently..Finally,.the.lexibility.of.
DNA.vaccines—in.terms.of.modifying.gene.sequences—has.allowed.for.increased.gene.
expression. and. the. induction. of. broader. immune. responses.. For. example,. codon. opti-
mization. has. been. used. to. increase. gene. expression. in. host. target. tissues;. codons. that.
are. preferentially. used. in. human. muscle. cells. can. be. incorporated. to. maximize. gene.
